2.3.4.5- Tetra thiophene

Dichlorothiophene has become easily available through chlorination and dehydrochlorination of tetrahydrothiophened Another example of the aromatization of tetrahydrothiophene derivatives is the preparation of 3-substituted thiophenes by the reaction of 3-ketotetrahydrothiophene with Grignard reagents followed by the aromatization of the intermediate dihydrothiophene. Recent gas chromatographic analysis showed, however, that 2,3-dichlorothio-phene is the main product from the dehydrochlorination of tetra-chlorotetrahydrothiophene. 

Fig. 7 Selectivity to mono-, di-, tri-, and tetra-substituted thiophenes as a function of the molar ratio of bromine to thiophene [26]...

More activated substrates such as thiophene, produce a mixture of a,a -dithiophene mono-, di-, tri-, tetra-, and polysulfides. When both a-positions of thiophene are taken by methyl groups, a and a fused tricyclic product... 

Octahydrodibenzothiophene (73) has been prepared by the following sequence. Friedel-Crafts acylation of 4,5,6,7-tetra-hydrobenzo[6]thiophene with succinic anhydride (87%) or with the ester chloride of succinic acid followed by hydrolysis (80%), yields the keto acid (74). Huang-Minlon reduction of 74 followed by cyclization of the derived acid chloride with stannic chloride yields l-keto-1,2,3,4,6,7,-8,9-octahydrodibenzothiophene (53) (Section V,A). Reduction of 53 gives 73 as a solid (overall yield 32%). 

The reduction of thieno[3,2-6]thiophene-2,5-diaIdehyde or dithieno-[3,2-i 2, 3 -d]thiophene-2,6-dialdchyde with potassium in tetra-hydrofuran or 1,2-dimethoxyethane yields the corresponding anion-radicals, the ESR of which give information on the conformation of similar carbonyl compounds.Cation-radicals have also been studied (see Section IV). 

Dim yl-l/f,3/f-thieno[3,4-c]thiophene (142) with sodium periodate in methanol yields e 2-oxide (143) (91%X and 1,3,4,6-tetra-phenyl-lfl, 3fl-thieno[3,4-c]thiophene (147) behaves analogously to form 148 (96%). 

Methods of synthesis of 3-chloro- and 3,4-dichloro-thiophenes have usually involved tedious procedures in which tri- and tetra-chloro derivatives are dechlorinated by reductive or other methods. Gthanolic potassium hydroxide converted 2,3,4,5-tetrachlorothiophene into a 50 50 mixture of 2,4- and 3,4-dichlorothiophenes direct heating of the same tetrachloro substrate gave a mixture of 2,3- and 2,4-dichloro isomers (48JA1158). 3,4,5-Trichlorothiophene was readily prepared by the reaction of 1,1,2,3-tetrachloro-l,3-butadiene with sulfur (82JOU348). 

The product from the fluorination of thiophene over potassium tetrafluorocobaltate(III) varied, not surprisingly, with temperature.108 At 120 C, virtually the sole product was the dihydrothiophene 5, albeit in low yield (14%) this compound is obviously analogous to 2,2.5,5-tetra-fluoro-2,5-dihydrofuran from tetrahydrofuran and potassium tetrafluorocobaltate(IIl). At 350-370 °C, 5 is still a major product, but now seven others are also present, the main ones being 6-8 and the sulfur extruded product perfluorobutane. 

It is generally agreed that there is a common sequence of mechanistic pathways for all PASCs as shown earlier in Scheme 1. Though the partially hydrogenated thiophene intermediate is illustrated in that scheme as a tetrahydro derivative, it has been shown that this intermediate is, in reality, an equilibrium mixture of the tetra- and hexahydrodibenzothiophenes. The rate of equilibration is at least 10 times greater than the other associated rates. Thus, the pair can be treated as a single kinetic species (26). 

Dihydrothiophene derivatives have been utilized for the synthesis of both tetra-hydrothiophenes and thiophenes. One of the syntheses of biotin has made extensive use of substituted 2,5-dihydrothiophenes (77JOC1630) stereospecific catalytic reduction to the tetrahydro level was reserved until a late stage (Scheme 213). The stability of the intermediate 2,5-dihydrothiophenes was ensured by proper choice of substituents at the 3- and 4-positions. 

UV spectra of tri-,104,134,136,139,187 tetra-,81 134,136,139,187,188 and pentaalkylbenzo[6]thiophenes139 and of several of their monohalo derivatives81 have been recorded. Spectra have been given for substituted dimethoxy-189 and 5,6-methylenedioxybenzo[6]thio-phenes,189,190 and 6-substituted 2,3-dibromobenzo[6]thiophenes.77... 

A mixture of hydrogen sulfide and hydrogen chloride effects cycli-zation of 2-propynylcyclohexanone (44) to 2-methyl-4,5,6,7-tetra-hydrobenzo[6]thiophene (45) (69%).260 Treatment of 46 with either hydrogen sulfide or carbon disulfide also affords 45, but in lower yields. A 5% yield of 45 is obtained, together with 10% 2-methyl-4,5,6,7-tetrahydrobenzofuran, when phosphorus pentasulfide is used to effect cyclization of 44. 

Tetrahydrobenzo[6]thiophene may be prepared by Clem-mensen355 or Huang-Minlon194,356,436 reduction of 4,5,6,7-tetra-hydrobenzo[6]thiophen-4-one (103) or by Wolff-Kishner reduction of... 

The synthesis of 4,5,6,7-tetrahydrobenzo[6]thiophen-4-one and -7-one has been described in Section IV, G 4-methyl-4,5,6,7-tetra-hydrobenzo[6]thiophen-5-one is obtained on oxidation of 136 (R = Me) with per benzoic acid.438... 

Tetrahydrobenzo[6]thiophene-2-carboxaldehyde condenses with compounds containing a CH2CN group.436 2-Acetyl- and 2-propionyl-4,5,6,7-tetrahydrobenzo[6]thiophene undergo the Pfitzinger reaction with isatins.436 Attempts to prepare 2-cyano-4,5,6,7-tetra-... 

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